HCC is considered to be a terminally-ill disease and currently there is little progress toward the discovery of efficient therapies leading to its recession. This is largely due to the lack of a method for an earlier diagnosis and the lack of information on the phenotypic changes associated with the development of HCC. Changes in gene expression during the genesis of HCC are largely unknown. Efforts to identify gene expression profiles will contribute to the establishment of novel markers with potential diagnostic and prognostic value for HCC. Analysis of these genes would provide further understanding of the genesis of liver cancer and provide further insights into designing strategies for HCC-directed molecular therapy. Now we are using SAGE to explore the potential cellular genes that are disregulated in primary human hepatocytes by HBx or HC-core. Specifically, we plan to identify a potential group of genes whose expressions are specifically (i.e., hepatocytes vs. fibroblasts) and abnormally regulated by HBx or HC-core in primary hepatocytes derived from healthy donors. The revealed expression changes in the genes of interest are used to compare with the gene expression profile from HBx-positive or HCV-positive HCC. This approach would allow us to identify potential genes that are related to HBV and HCV-mediated oncogenesis. We are also utilizing the NCI Human OncoChip Genes microarray to compare the expression profiles in primary HCC and metastatic HCC from Shanghai, China. These data will be used to compare the gene expression patterns of HCC from different geographic areas that differ in the status of HBV or HCV, and to identify their change patterns during the progression from primary tumors to metastatic lesions of HCC. We are currently examining gene expression profiles of HCC samples from the US. The HCC samples from the US are currently being collected through the cooperative Human Tissue Network, funded by the National Cancer Institute. - SAGE, microarray, hepatocellular carcinoma, hepatitis B virus, hepatitis C virus, - Human Tissues, Fluids, Cells, etc.